Respiratory Failure, Wounds and Injuries
Conditions
Brief summary
A randomized, multi-center trial involving critically-ill patients comparing conventional, manual control of inspired oxygen (FiO2) within a target range, with a computer-controlled, closed-loop FiO2 delivery using a continuous ventilator.
Detailed description
The trial will use a proportional-integral-derivative (PID) type controller for automatic adjustment of FiO2 to maintain the SpO2 within a target range, based on continuous use of pulse oximetry. Intubated subjects will be randomized to either manual control of FiO2 or closed-loop control of FiO2, during a 12-hour period. The PCLC is designed to respond to acute hypoxemia (SpO2 \<88%) within seconds while preventing hypoxemia and minimizing exposure to excessive inspired oxygen levels.
Interventions
DEVICEClosed Loop Control Ventilation
Closed loop control ventilation using ZOLL 731 ventilator with physiologic closed-loop control software
DEVICEManual Control Ventilation
Manual control ventilation using ZOLL 731 ventilator
Sponsors
United States Air Force
Zoll Medical Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* The subject's legally authorized representative will provide signed and dated informed consent. * Age 18 - 65, inclusive. * Admission to a surgical or neurosurgical intensive care unit following traumatic injury or acute surgical illness * Requirement for endotracheal intubation * Requirement for mechanical ventilation * Patient is currently receiving inspired oxygen concentration (FiO2) \>=40%
Exclusion criteria
* Age under 18 or over 65 * Isolated or severe head injury (Glasgow Coma Scale = 6 or less) with expected survival less than 24 hours * Brain death * Anticipated survival less than 48 hours * Pregnant female * Patient in whom a pulse oximeter cannot detect a reliable signal due to hypotension, hypothermia, or other injury * Known carbon monoxide poisoning * Uncontrolled diabetic * Patient who is unable to maintain SpO2 level of 88% at an FiO2 of 100% due to their medical condition. (NOTE: Being in the trial would impose no additional risk to a patient who presents with this condition however, data from a patient presenting with this pathophysiology would not provide insight into the performance of the controller as it would simply maintain that patient on an FiO2 of 100%.) * Patient with chronic hypercarbia. * Patient where a physician believes that FiO2 PCLC could be detrimental to the management of the patient. * Prisoner * SpO2 to SaO2 difference \>4% * Patient with core temperature \<35 C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Duration With Oxygen Saturation (SpO2) Within Target Range [Time Frame: 12 Hours] | 12 hours | Relative duration is (time within SpO2 target of 92-96%)/12 hours where higher value demonstrates better ability of FiO2 control method to maintain appropriate oxygen saturation. Relative time the patient's SpO2 was maintained within target over the 12 hours on the study device, calculated as total time each patient had SpO2 within the 92 - 96% range divided by 12 hours with arcsin square root transformation |
| Number of Participants With SpO2 Less Than 88% at Anytime While on Study Device | 24 hours after intervention | Number of participants with SpO2 less than 88% at anytime while on study device |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Duration of Time With SpO2 92 to 96% When FiO2 is Greater Than 21% and SpO2 is Greater Than or Equal to 92% When Fi02 Relative Duration With Oxygen Saturation (SpO2) Within Target Range [Time Frame: 12 Hours] | 12 hours | Relative duration is (time within SpO2 target of either a) 92-96% when FiO2 is greater than 21% or b) greater than or equal to 92% when FiO2 equals 21%)/12 hours where higher value demonstrates better ability of FiO2 control method to maintain appropriate oxygen saturation. Relative time the patient's SpO2 was maintained within target over the 12 hours on the study device, calculated as total time each patient had SpO2 within the range divided by 12 hours with arcsin square root transformation |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Closed Loop Control Ventilation automatic adjustment of the ZOLL 731 ventilator FiO2 by the closed loop control software
Closed Loop Control Ventilation: Closed loop control ventilation using ZOLL 731 ventilator with physiologic closed-loop control software | 104 |
| Manual Control Ventilation manual adjustment of the ZOLL 731 ventilator FiO2 by the treatment team based on physician order
Manual Control Ventilation: Manual control ventilation using ZOLL 731 ventilator | 102 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Physician Decision | 4 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Closed Loop Control Ventilation | Total | Manual Control Ventilation |
|---|---|---|---|
| Age, Continuous | 37.2 years STANDARD_DEVIATION 13.07 | 38.4 years STANDARD_DEVIATION 13.66 | 39.6 years STANDARD_DEVIATION 14.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 27 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 88 Participants | 174 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 48 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants | 23 Participants | 10 Participants |
| Race (NIH/OMB) White | 65 Participants | 132 Participants | 67 Participants |
| Region of Enrollment United States | 104 Participants | 206 Participants | 102 Participants |
| Sex: Female, Male Female | 22 Participants | 45 Participants | 23 Participants |
| Sex: Female, Male Male | 82 Participants | 161 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 104 | 2 / 102 |
| other Total, other adverse events | 24 / 104 | 17 / 102 |
| serious Total, serious adverse events | 0 / 104 | 9 / 102 |
Outcome results
Primary
Number of Participants With SpO2 Less Than 88% at Anytime While on Study Device
Number of participants with SpO2 less than 88% at anytime while on study device
Time frame: 24 hours after intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control Ventilation | Number of Participants With SpO2 Less Than 88% at Anytime While on Study Device | 31 Participants |
| Manual Control Ventilation | Number of Participants With SpO2 Less Than 88% at Anytime While on Study Device | 49 Participants |
Primary
Relative Duration With Oxygen Saturation (SpO2) Within Target Range [Time Frame: 12 Hours]
Relative duration is (time within SpO2 target of 92-96%)/12 hours where higher value demonstrates better ability of FiO2 control method to maintain appropriate oxygen saturation. Relative time the patient's SpO2 was maintained within target over the 12 hours on the study device, calculated as total time each patient had SpO2 within the 92 - 96% range divided by 12 hours with arcsin square root transformation
Time frame: 12 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control Ventilation | Relative Duration With Oxygen Saturation (SpO2) Within Target Range [Time Frame: 12 Hours] | 0.53 arbitrary units | Standard Deviation 0.37 |
| Manual Control Ventilation | Relative Duration With Oxygen Saturation (SpO2) Within Target Range [Time Frame: 12 Hours] | 0.61 arbitrary units | Standard Deviation 0.36 |
Secondary
Relative Duration of Time With SpO2 92 to 96% When FiO2 is Greater Than 21% and SpO2 is Greater Than or Equal to 92% When Fi02 Relative Duration With Oxygen Saturation (SpO2) Within Target Range [Time Frame: 12 Hours]
Relative duration is (time within SpO2 target of either a) 92-96% when FiO2 is greater than 21% or b) greater than or equal to 92% when FiO2 equals 21%)/12 hours where higher value demonstrates better ability of FiO2 control method to maintain appropriate oxygen saturation. Relative time the patient's SpO2 was maintained within target over the 12 hours on the study device, calculated as total time each patient had SpO2 within the range divided by 12 hours with arcsin square root transformation
Time frame: 12 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control Ventilation | Relative Duration of Time With SpO2 92 to 96% When FiO2 is Greater Than 21% and SpO2 is Greater Than or Equal to 92% When Fi02 Relative Duration With Oxygen Saturation (SpO2) Within Target Range [Time Frame: 12 Hours] | 0.92 arbitrary units | Standard Deviation 0.34 |
| Manual Control Ventilation | Relative Duration of Time With SpO2 92 to 96% When FiO2 is Greater Than 21% and SpO2 is Greater Than or Equal to 92% When Fi02 Relative Duration With Oxygen Saturation (SpO2) Within Target Range [Time Frame: 12 Hours] | 0.83 arbitrary units | Standard Deviation 0.36 |